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this is a huge huge breakthrough -- if you look at the history of hiv research they have been trying to use gp120 to solve this epidemic and they kept failing and now they discovered how and why, this is an amazing event, one tiny part of the virus cannot change so that makes sense -- the possiblities are endless for treatments and hope -- new meds, new vaccines, new anti-bodies many new directions in research

if you look at all the early vaccines that failed they all used gp120 now they can repeat them with tiny slight change and they might have complete success

Wednesday, July 16, 2008 (Washington)University of Texas researchers led by Indian American Sudhir Paul have pinpointed the Achilles heel in the protective mechanism of HIV, the virus that claims millions of lives worldwide when it develops into AIDS. The finding may give hope to millions of HIV positive people.

The weak spot is hidden in the HIV envelope protein gp120. This protein is essential for HIV attachment to host cells, which initiate infection and eventually lead to AIDS.

The Achilles heel, a tiny stretch of amino acids numbered 421-433 on gp120, is now under study as a target for therapeutic intervention.

Paul, who led the research and co-authored the paper said: ''Unlike the changeable regions of its envelope, HIV needs at least one region that must remain constant to attach to cells.''

If this region changes, HIV cannot infect cells, he said, adding: ''Equally important, HIV does not want this constant region to provoke the body's defence system.'' So, HIV uses the same constant cellular attachment site to silence B lymphocytes - the antibody producing cells. The result is that the body is fooled into making abundant antibodies to the changeable regions of HIV but not to its cellular attachment site.

''Immunologists call such regions super-antigens. HIV's cleverness is unmatched. No other virus uses this trick to evade the body's defences,'' said Paul, an alumni of the All India Institute of Medical Sciences in New Delhi.

For the same reason, no HIV preventive vaccine that stimulates production of protective antibodies is available.

First reported in the early 1980s, HIV has spread across developing countries, infecting some 33 million people by 2007 according to a WHO report. Paul's group has engineered antibodies with enzymatic activity, also known as abzymes, which can attack the Achilles heel of the virus in a precise way.

''The abzymes recognise essentially all of the diverse HIV forms found across the world. This solves the problem of HIV changeability. The next step is to confirm our theory in human clinical trials,'' Paul said. A single abzyme molecule deactivates thousands of virus particles, permanently, unlike regular antibodies that act only against a single virus particle, and their anti-viral HIV effect is weaker.

''The work of Paul's group is highly innovative. They have identified antibodies that, instead of passively binding to the target molecule, are able to fragment it and destroy its function,'' said Steven J. Norris of the University of Texas Medical School. ''Their recent work indicates that naturally occurring catalytic antibodies, particularly those of the IgA subtype, may be useful in the treatment and prevention of HIV infection,'' he said. The abzymes are derived from HIV negative people with the autoimmune disease lupus and a small number of HIV positive people who do not require treatment and do not get AIDS. These findings have appeared in the latest issue of the journal Autoimmunity Reviews.

The weak spot is hidden in the HIV envelope protein gp120. This protein is essential for HIV attachment to host cells, which initiate infection and eventually lead to Acquired Immunodeficiency Syndrome or AIDS. Normally the body’s immune defenses can ward off viruses by making proteins called antibodies that bind the virus. However, HIV is a constantly changing and mutating virus, and the antibodies produced after infection do not control disease progression to AIDS. For the same reason, no HIV preventative vaccine that stimulates production of protective antibodies is available.

The Achilles heel, a tiny stretch of amino acids numbered 421-433 on gp120, is now under study as a target for therapeutic intervention. Sudhir Paul, Ph.D., pathology professor in the UT Medical School, said, “Unlike the changeable regions of its envelope, HIV needs at least one region that must remain constant to attach to cells. If this region changes, HIV cannot infect cells. Equally important, HIV does not want this constant region to provoke the body’s defense system. So, HIV uses the same constant cellular attachment site to silence B lymphocytes - the antibody producing cells. The result is that the body is fooled into making abundant antibodies to the changeable regions of HIV but not to its cellular attachment site. Immunologists call such regions superantigens. HIV’s cleverness is unmatched. No other virus uses this trick to evade the body’s defenses.”

Paul is the senior author on a paper about this theory in a June issue of the journal Autoimmunity Reviews. Additional data supporting the theory are to be presented at the XVII International AIDS Conference Aug. 3-8 in Mexico City in two studies titled “Survivors of HIV infection produce potent, broadly neutralizing IgAs directed to the superantigenic region of the gp120 CD4 binding site” and “Prospective clinical utility and evolutionary implication of broadly neutralizing antibody fragments to HIV gp120 superantigenic epitope.”

First reported in the early 1980s, HIV has spread across the world, particularly in developing countries. In 2007, 33 million people were living with AIDS, according to a report by the World Health Organization and the United Nations.

Paul’s group has engineered antibodies with enzymatic activity, also known as abzymes, which can attack the Achilles heel of the virus in a precise way. “The abzymes recognize essentially all of the diverse HIV forms found across the world. This solves the problem of HIV changeability. The next step is to confirm our theory in human clinical trials," Paul said.

“The work of Dr. Paul’s group is highly innovative. They have identified antibodies that, instead of passively binding to the target molecule, are able to fragment it and destroy its function. Their recent work indicates that naturally occurring catalytic antibodies, particularly those of the IgA subtype, may be useful in the treatment and prevention of HIV infection,” said Steven J. Norris, Ph.D., holder of the Robert Greer Professorship in the Biomedical Sciences and vice chair for research in the Department of Pathology and Laboratory Medicine at the UT Medical School at Houston.

The abzymes are derived from HIV negative people with the autoimmune disease lupus and a small number of HIV positive people who do not require treatment and do not get AIDS. Stephanie Planque, lead author and UT Medical School at Houston graduate student, said, “We discovered that disturbed immunological events in lupus patients can generate abzymes to the Achilles heel of HIV. The human genome has accumulated over millions of years of evolution a lot of viral fragments called endogenous retroviral sequences. These endogenous retroviral sequences are overproduced in people with lupus, and an immune response to such a sequence that resembles the Achilles heel can explain the production of abzymes in lupus. A small minority of HIV positive people also start producing the abzymes after decades of the infection. The immune system in some people can cope with HIV after all.”

Carl Hanson, Ph.D., who heads the Retrovirus Diagnostic Section of the Viral and Rickettsial Disease Laboratory of the California Department of Public Health, has shown that the abzymes neutralize infection of human blood cells by diverse strains of HIV from various parts of the world. Human blood cells are the only cells that HIV infects.

“This is an entirely new finding. It is a novel antibody that appears to be very effective in killing the HIV virus. The main question now is if this can be applied to developing vaccine and possibly used as a microbicide to prevent sexual transmission,” said David C. Montefiori, Ph.D., director of the Laboratory for AIDS Vaccine Research & Development at Duke University Medical Center. The abzymes are now under development for HIV immunotherapy by infusion into blood. They could also be used to guard against sexual HIV transmission as topical vaginal or rectal formulations.

“HIV is an international priority because we have no defense against it,” Paul said. “Left unchecked, it will likely evolve into even more virulent forms. We have learned a lot from this research about how to induce the production of the protective abzymes on demand. This is the Holy Grail of HIV research -- development of a preventative HIV vaccine.”

Major contributors to the research from the UT Medical School include Yasuhiro Nishiyama, Ph.D., and Hiroaki Taguchi, Ph.D., both with the Department of Pathology and Laboratory Medicine, and Miguel Escobar, M.D., of the Department of Pediatrics. Maria Salas and Hanson, both with the Viral and Rickettsial Disease Laboratory, contributed.

The research was funded by the National Institutes of Health and the Texas Higher Education Coordinating Board.

MUHC and CHUM researchers demonstrate how two specific genes are involved in an innate resistance to HIV infection.

Some people may be naturally resistant to infection with HIV, the virus that causes AIDS. The results of a study conducted by Dr. Nicole Bernard of the Research Institute of the McGill University Health Centre (MUHC) bring us closer to a genetic explanation. Her study findings were published on July 16 in the journal AIDS.

The simultaneous expression of certain versions of two specific genes called KIR3DL1 and HLA-B*57 is thought to be at the root of some cases of this innate resistance to HIV infection. Depending on which versions of these two genes the patient has, he or she will resist HIV infection or develop AIDS at a slower rate.

These results were obtained by comparing the genetic profiles of people undergoing primary HIV infection ( in their first year of infection) to those repeatedly exposed to HIV but non-infected. The group of exposed but non-infected patients came from a cohort studied by Dr. Julie Bruneau of the Centre hospitalier de l'Université de Montréal. The cohort of primary HIV infected patients is studied by Dr. Jean-Pierre Routy, from the MUHC. Analyses show that the "good" versions of both genes were present in 12.2% of exposed but non-infected subjects versus only 2.7% in patients in primary HIV infection.

As of yet, no study has clearly described the mechanism of this protection. The KIR3DL1 gene codes for a receptor on the surface of the immune system's natural killer (NK) cells, which when activated destroy infected cells in the body. The HLA-B*57 gene codes for a protein normally found on the surface of all body cells that binds the KIR3DL1 and dampens NK cell activity. The most likely hypothesis is that HIV prevents the HLA-B*57-encoded protein from being expressed on the surface of the infected cells, making it unavailable to bind KIR3DL1. As a consequence, the NK cells retain their activity and destroy the virus-infected cells.

As this mechanism can occur very soon after the virus has started to infect the body cells, people carrying those versions of the 2 genes may be able to destroy more efficiently the infected cells following exposure to HIV, thus lowering their chances of developing AIDS.

"More research is needed to determine the exact mechanism behind the protection we have observed, but these findings have revealed a promising avenue," according to Dr. Bernard.

This study opens the way for new ideas in the fight against HIV infection. "In the future, our findings could be used to somehow 'boost' the innate immune system and thus fight the virus as soon as it enters the body," said Dr. Bernard.

Simultaneous expression of certain versions of KIR3DL1 and HLA-B*57 genes, which has been associated with a reduced risk of HIV progressing to AIDS, also lowers the risk of HIV infection in exposed uninfected individuals, according to a group of researchers.

The strongest protection from disease progression in KIR3DL1 homozygotes (3DL1 hmz) is the coexpression of HLA-B*57 and a set of KIR3DL1 genotypes (3DL1*h/*y) lacking alleles expressed at low levels on natural killer cells. The scientists decided to evaluate whether this allele combination could also influence resistance to infection. The genetic distribution of 3DL1*h/*y and HLA-B*57 was compared in 41 HIV-exposed uninfected and 186 recently HIV-infected KIR3DL1 homozygotes.

The researchers found that 12.2% HIV-exposed uninfected people and 4.3% of individuals in the primary infection cohort expressed HLA-B*57. The percentage of 3DL1*h/*y carriers were similar in both populations. The 3DL1*h/*y-HLAB*57 combined genotype was more frequent in exposed uninfected individuals (12.2%) than individuals with primary infection (2.7%).

The investigators thus concluded that the coexpression of 3DL1*h/*y and HLA-B*57 contributes to a lower risk of developing HIV when exposed to the virus.

The study was conducted by scientists at the Research Institute of the McGill University Health Centre and University of Montreal Hospital Centre, Montreal. It is published in the July 16 issue of journal AIDS.

the great thing is i think that these are already available for treatment they dont have to invent the drugthey already have the abzymeand all they have to do is test it in humans

as we all know to find a non toxic drug molecule is extremely long and difficultbut these new monoclonal antibodies which were the great hope of medicine for last 20 years are finally becoming available and discovered

it looks so simple but imagine trying to build a enzyme at the molecular level that is perfect shape to do something in the body

There seems to be a lot of internet discussion about this finding. It sounds perfectly logical to me, but then I'm not a virologist. I wonder what this might lead to in the future. Let's hope for the potential in this one.

the great thing is i think that these are already available for treatment they dont have to invent the drugthey already have the abzymeand all they have to do is test it in humans

Wrong. The active chemicals were derived from human samples at great expense. Mapping their composition may be a fairly simple exercise, but producing them for mass distribution will be a challenge. Then, testing them in animals and humans will present another hurdle.

This is a message I post from time to time as a general warning. A few of our regulars in this Research Forum, notably John2038 and bimazek, have a tendency to view each potential new AIDS therapy as a possible cure. Neither of them are on treatment, and neither is an "expert" in HIV research (in the opinion of our own experts at AIDSmeds.com).

They both over-hype every press release or early study they read about, and fail to keep things in proper perspective. While the news above is certainly promising, it is way too soon for this level of optimism. The history of AIDS research is littered with therapies that sound just as good at first, but don't pan out later in the larger clinical trials.

Jeez, some of you really do fall easily with nothing more than a press release and some bad local news reporting. I'd like to share something. This has been discussed on the leading listserve that U.S. AIDS treatment activists use to discuss the latest research.

Here's a quote from Martin Delaney, the founder of Project Inform:

The general assessment I’ve gotten from scientists I trust most is that this a pile of hooey, yet another bit of science by press release coming out of Texas lately. It seems to be in the blood there, or maybe the university system has hired a PR firm and is trying to figure out what to do with it. The notion that there is some small unchanging region of the HIV envelope, usually in the V3 loop, is something that’s reported about once every year, each time claiming to have found the holy grail, or is it the holy loop? I’ve lost count of the number of times I’ve heard about “the Achilles heel” of HIV, each time it’s something different. There are indeed some highly conserved regions of HIV that are targets in vaccine development, but as far as I know, not by this group. Most people I’ve asked have never heard of these people and they certainly about part of the usual crowd of HIV researchers. It’s hard to say whether they’re talking about a treatment or a vaccine. Either way, they don’t seem to be mentioning any of the things normally associated either with drug testing or vaccine development. If it’s about vaccines, what’s going on in the animal studies? They sound like they just want to jump into humans. If it’s for a drug, what does the FDA have to say? Have their claims been verified by anyone? In one sentence, he’s quoted as saying it’s the key to a preventive vaccine. In the next sentence, he says “if we can get the viral loads down to a manageable level, that will preclude the need for these conventional drugs." So what is the goal here, a treatment? A preventive vaccine? A vaccine that would just reduce the viral set point? We already have excellent controls for getting the viral load reduced.

And why is the story bracketed by tales of a patient who is on conventional antiviral therapy and doing very well?

This article tells us nothing, and maybe it’s because there really is nothing tell us. If they really have something new or different, there’s a well established way for presenting for review by the scientific community. Press releases like this are not the way.

So go ahead, and yell your Hallelujahs. I'm going to save my praise for the real science coming out of Mexico City next week.

What I think they are saying is that it has the possiblity of both a preventative vaccine for those not infected and also a way to control the virus for people already infected. Or maybe they just don't know yet until they get to in vivo trials... which is quite the norm or so it seems. They also stated that in vitro and animal trials have already been conducted... so I'm assuming this infomation is sitting there and being reviewed by someone. The interviewers may have left out some pertinent information that would somewhat ease our doubts, but I still think it looks promising. And I will never lose optimism just because something hasn't been verified yet. Sometimes we need to hype it up in order to get the word out... and attract funds from different groups to take it to larger scaled trials... eventually, teamed up with pharma companies... right? But, of course, we know there is a specific set of rules and guidelines to take the appropraite steps in developing vaccines and drugs. We do have excellent controls for getting the viral load reduced but there is still a chance of resistance and toxicities... as we know. And if a vaccine would allow for us to control this virus by taking it just once a year or even less then that would be a blessing for many... especially those in developing countries who can't get their hands on drugs every day. So let their be hope of something better, and hopefully, when this is looked at in Mexico City it will have more meaning within the scientific community... meaning that will ease the pain of so many critics that seem to have so much first hand experience in research and development. I don't know these people... but I like them for their bold attempt to destroy one of the most deadliest viruses in the history of mankind... whether the research brings us to a new beginning or not. Here comes the censoring.

"...health will finally be seen not as a blessing to be wished for, but as a human right to be fought for." Kofi Annan

Nymphomaniac: a woman as obsessed with sex as an average man. Mignon McLaughlin

HIV is certainly character-building. It's made me see all of the shallow things we cling to, like ego and vanity. Of course, I'd rather have a few more T-cells and a little less character. Randy Shilts

Censoring? Where? Who? What's all this crap about censoring all of sudden?

Nobody is censoring anything in this thread, as far as I can tell. Just because you're free to express misguided opinions, doesn't mean you can't be criticised and corrected. Which is what's happened here.

I'm going to save my praise for the real science coming out of Mexico City next week.

CERTAINLY!!!

Many of the leading lights in the battle against AIDS from all over the world are similarly disinclined to attend [Mexico City International AIDS Conference], saying they are not able to join in celebrating the creation of a vast, multibillion dollar AIDS treatment industry, employing hundreds of thousands of individuals worldwide that serve as a vested lobby on behalf of a prolonged medical approach to a virus that ought to be eliminated entirely from the pantheon of threats to Humanity.

[...]

it is troubling that formerly militant activists, United Nations agency leaders, government health officials, the American foreign policy establishment, religious leaders, scientists and physicians fail to see AIDS treatment for what it is: A stop-gap measure to tide humanity over until we can collectively reach what ought to be our real goal - stopping HIV's spread, entirely. On an individual basis living with AIDS is a proper goal; on a population basis it is catastrophic.

The slogan of the first 15 years of the pandemic was, "Until there is a cure!" Today it seems the global health leadership of the world is satisfied with, "Until there is lifelong drug therapy for everybody, and no prevention strategy!" A dangerous sentiment is sweeping over the AIDS establishment, calling for elimination of all funding for HIV vaccine research and prevention programs, shifting those dollars, euros and yen to expanding HIV treatment.

It is inconceivable that children coming of age in 2021 - 40 years after the recognized start of this epidemic - will feel gratitude toward today's leaders for saddling them with a still widely circulating virus. If today's HIV-treatment model is viewed as an interim step - keeping people alive until a cure and vaccine are discovered - its funding and expansion make sense not only morally, but also as a practical matter of economics and foreign policy - but only if a massive commitment to funding searches for both a vaccine and cure for HIV are sustained for years to come. (Even the cancer lobby recognizes the needs for both oncology treatment access and ongoing curative research.)

It's not about toughening up... it's about having some compassion whether you believe its misguided or not.

I think the original idea for the "research forum" was to discuss/ analyze new studies, trials etc. etc. I'd suggest you reread Peter's posts again for this thread. I think he was spot on. For some of us who have lived with this for over 20 years have we've come to recognize that there is and has been lot of hype out there. When a lot of these research studies hit the mainstream media, more than likely they have run their course.

It's wonderful to be able to discuss the possibilities of new research, but most of the "stuff" that has been posted here is just in very very early stages and most of it will not go anywhere.

the word compassion gets thrown around a lot and most people aren't using it correctly. You might have empathy for someones worries or suffering, but you don't enable their continued suffering. I think "toughening up" is very appropriate and compassionate. It's wonderful to have hope but don't hang on to glimpses of some ill-fated research.

Laurie is a good writer, and makes some good point, but I think misses one trick, namely the rising cost of ARVs is a matter of political will, if it's gonna be that expensive at home and abroad it is surely not beyond the whit of man or mona to appropriate the intellectual property and reduce the price of treatment to a few cents? Or perhaps it is. << bit off-topic this

Vaccines are a shit crock proposition for HIV. Eradication of HIV from the body is gonna be a many fronted, long war. More money for a decent chemical prevention technology, microbicide, depot antiviral, 1 dose pill, etc please.

I agree with Peter, HAART solves, for the most problem, the immediate question of a slow, painful death, morphine notwithstanding (I am allergic).The death rate of HIV+ folks in the UK has more or less been flatline and low rate since the arrival of PIs in 1996. It's a bloody good advance.

The meds we have available at the moment are good for slowing the progression of HIV in the majority of people but there is one problem - what about the people who don't have access to good, regular medication. In the poorer countries (where most of the HIV+ cases are) this is very common and the lack of adherence to meds is a major factor in the development of strains of HIV that are drug resistant in these regions. I think this is why finding a vaccine is so important, because adequate treatment can never be relied upon in resource limited settings - it is much easier to just poke everyone once or twice with a needle than to find them a lifetime supply of drugs.

I think everyone should wait and see how the clinical trials pan out for this new treatment before getting too excited. Be cautiously optimistic!!!

Actually, Anna, from all that I've heard over the years, adherence has been less of an issue in under-developed countries than in the developed countries, from all I've heard. It's a common misperception that's been shown to be false.

This is the 2nd time you've said this in the forums. I believe there is data showing that many of the new patients on ARVs in Africa have some of the best adherence rates in the world.

I'm sorry I'm not providing links to the research that has shown this, but since you didn't either, why don't you do some Web searching on this for us both.

i think one issue is the title of this forum is research news and studies

there should be three completely separate sections

1 clinical trials

2 research on haart

3 future research directions

then the things that are close

like clinical trials new things that people can actually can be part of can be seen

then all the very complex 2 research on haart on what is good and better can have separate section

and then

for hope and dreaming of a cure or hope of better meds a section called

3 future research directions or research directionsnew hiv science or something along those lines

it is not fair to put

3 future research directions or research directionsnew hiv science or something along those lines

which can be 5 to ten years away from realityin same section as trials

and haart research

just a thought

everyone wants to have hope that there is going to be newer meds and ALSO newer science that may make things better

also

clinical trials are for right now

something REAL today

it is not fair to have today tomarrow and 5 to ten years from now lumped together

in same area

just a thought

i think it would help

some like science some only like science if it is REAL results TODAY that can be tried

some like to find out what ways to make haart better

innovation always comes out of the blue

there is tremendous jeleousy in science

if china finds a great thingwho knows what is the future

regarding this discovery

there are facts

lupus patients do not seem to progress to aids they seem to be LTNP is that true can someone verify

i posted on lupus patients numerous times in past --- this is a key this is a fact or is it

also

there are one million antibodies in every human even healthy ones, they are provided by what we were exposed to and what are ancestors were exposed to

another fact seems to be

there are weak antibodies to the gp120 region of hiv that comes from a proto retro virus from 65 million years ago and is in saliva of all healthy humans who have not been exposed to hiv -- that is one reason it is hard to get hiv orally

is this a fact or not

i think it is a fact

if this weak antibody can be stimulated that could do some good

are there any journalists or writers who can make a phone call to these scientists and find out any more info?

As the 17th annual AIDS conference opens in Mexico City on Sunday, Aug. 3, DW-WORLD.DE spoke to German AIDS researcher Hans Jaeger who says he's optimistic about finding a cure to the deadly virus.

DW-WORLD.DE: More than 25 years after the emergence of the AIDS epidemic what are the chances of finding a cure to what has largely become a treatable disease?

Dr. Hans Jaeger: We can say that at the beginning we were working with a disease that was not treatable at all, and the majority of patients died relatively quickly. Then starting in the middle of the 90s -- due to a variety of improvements such as a better recognition of how the virus spreads and the ability to measure the virus in the blood but particularly thanks to new medicines to develop treatments -- the disease became more treatable.

Our next goal is a cure -- the medical word for it would be eradication. That means having the ability to remove the virus from the body or to suppress it to the point where it can no long do any damage. That is our main goal at the moment.

I personally believe we will reach this goal because the progress we are making against HIV is much larger than in other comparable serious diseases. At the moment we have medicines that are better than ever at treating patients and possibly even healing them.

I did some looking around and you are right, access to the drugs have been rapidly expanding in resource limited settings over the past couple of years (edit) and the research shows that adherence to meds in these regions is a lot higher than we previously thought so I stand corrected

However, adherence to medication is still a problem in a large section of the HIV+ population in resource limited settings. There is also a problem with the medication itself, regardless of adherence (in these settings) and I will explain this (I promise I'll reference this time lol ).

The problem is largely due to Tuberculosis. A third of HIV+ people worldwide are co-infected with Mycobacterium tuberculosis (the bacteria that causes TB). In Sub-Saharan Africa TB is by far the most common OI. Studies from Sub-Saharan Africa have recorded HIV seroprevalence rates of 50 to 70% in patients with tuberculosis. Because TB is so common OI in these countries, coadministration of antitubercular and antiretroviral agents is very common. This coadministration creates a number of problems:

Firstly, drug adherence is reduced because the antiretroviral and TB drugs have some nasty overlapping toxicities. This causes unpleasant and sometimes serious side effects (like human immune reconstitution inflammatory syndrome).

Secondly (and this is independent of adherence), coadministration of TB and HIV drugs also result in a loss of antiretroviral activity (molecular mechanisms of rifampin, the standard TB drug, cause reduced concentrations of nonnucleoside reverse transcriptase inhibitors and particularly protease inhibitors) and the development of drug resistance.

Thirdly, the use of intermittent rifamycin (TB drug) in treating HIV-associated TB is associated with acquired R resistance (the article proposes this is due to to lower absorption of the drug in HIV+ people - seems that they achieve lower concentrations of the orally administered first-line TB drugs). There are ways around this, but they are expensive, and not always practical.

These three problems often necessitate discontinuation of therapy and increase the risk of nonadherance to either the HIV, TB or both classes of drugs.

There are ways to reduce these problems (like drug regiments that treat HIV and TB but don't have as much overlapping toxicity) - but in these resource limited settings individual patient assessment and treatment are at the moment impractical because limited antiretroviral and TB treatment regiments are available, fixed-dose combination formulations of both antiretroviral and TB drugs are commonly used and the treatment programs are usually administered by staff without specialised training so the capacity for monitoring treatment efficacy and toxicity are minimal.

Also, in many regions of Africa at the moment there is a massive problem with multi-drug resistant (MDR) and extensively drug resistant (XDR) strains of TB. On it's own, infection with these strains of TB is difficult to treat. But combined with HIV infection, these strains of TB are deadly. Incidentally, it is widely believed that these drug resistant strains have arisen from non-compliance with medication (like in the situations described above with the antiretroviral and TB drugs) so it's all linked. (I read this in a 2008 article http://www.ncbi.nlm.nih.gov/pubmed/18276863)

With children there are even more issues than complications with coinfection with TB to consider - the effects of ART on development, we also have a lack of information about the pharmacokinetics of ART in malnourished children - it seems intuitive that this would affect absorption. Also, the article by Callens et al proposes that in the long term, treatment success might be negated due to lower rates of viral suppression in children and the accumulation of resistance mutations. (I got this information from the following 2008 review article - http://www.ingentaconnect.com/content/ftd/eri/2008/00000006/00000002/art00007)p.s I love review articles they do all your work for you lol

I think these are the main issues, but I really only researched the problems with TB and HIV so there may be others. Basically HIV drugs are working for people who don't have TB, live in regions where they are unlikely to get TB, and have access to good healthcare and doctors who can individually tailor their treatment. Unfortunately, the majority of people in the world infected with HIV do live in regions with a high TB incidence, many are already coinfected with TB (which is nearing a majority in ss Africa) and don't have access to such great healthcare and doctors.

I think these issues all highlight why it is so important that as well as developing new and improved treatment regiments - the researchers spend as much time and money (IMO more) looking for a vaccine or a cure for this disease, especially in view of these extensively drug resistant strains of TB, the incidence of which are rising.

p.s researching this was fun, interesting and scary all at the same time !!

SO true, the ego component is often unbearably annoying and frustrating and always gets in the way of the truth. That is why I am always wary of any affiliated scientist who rubbishes another's work especially if it will exceed the greatness of his own (or the sales of the company he works for...I know that sounds cynical but I really believe it is true). This is a main reason why I hate the privatisation of research - I mean who knows how many discoveries or advances in knowledge have been quietly shelved because they would have reduced profit margins. Privatisation is good because it funds but gah I guess it's a double edged sword type situation.

Maybe if certain leaders of the world took a few measly billion out of the 'bombing people into democracy' fund or the 'spying on their own people in the name of national security' fund we wouldn't have to rely so much on private companies to fund our research (expecting violent backlash to that comment lol)

while i'm glad you had such a "fun, interesting and scary" time researching some of hte many issues hiv-tb coinfection raises, i'm not sure that really proves your statement re adherence, which peter commented on

a big meta-analysis that i can think of that you might want ot look at would be "Adherence to antiretroviral therapy in sub-Saharan Africa and North America. A meta-analysis" by EJ Mills. JAMA aug 2006

Quote from: bimazek

lupus patients do not seem to progress to aids they seem to be LTNP is that true can someone verify...

dunno mr, i have a hard time sifting through the crazy in most of yr posts... but this lupus patient for one has deffo progressed to aids

a big meta-analysis that i can think of that you might want ot look at would be "Adherence to antiretroviral therapy in sub-Saharan Africa and North America. A meta-analysis" by EJ Mills. JAMA aug 2006

while i'm glad you had such a "fun, interesting and scary" time researching some of hte many issues hiv-tb coinfection raises, i'm not sure that really proves your statement re adherence, which peter commented on

a big meta-analysis that i can think of that you might want ot look at would be "Adherence to antiretroviral therapy in sub-Saharan Africa and North America. A meta-analysis" by EJ Mills. JAMA aug 2006

dunno mr, i have a hard time sifting through the crazy in most of yr posts... but this lupus patient for one has deffo progressed to aids

kate

I wasn't trying to be, insensitive - with my fun, interesting and scary comment - I find biology interesting, I can't help it. I'm pretty sure it's because I'm an obsessive hypochondriac. I was just speaking my mind, didn't mean to offend.

Studies show that the interactions between these two classes of drugs (commonly administered given the amount of people coinfected with HIV and TB in ssAFrica) reduces adherence, reduces efficacy of antiretrovirals and increases drug resistance in people who are co-infected with HIV/TB. About a third of people who are HIV+ are coinfected with TB so this is not a small issue. The evidence largely supports my view, I would never say prove, it's a big no no.

How did this not lend credit to my statement and my original point that therefore we need a vaccine? You didn't explain it, you just said it didn't. I didn't say there is no adherence at all, I said it was reduced.

I will admit though, from what Peter said and then reading this paper and the others I posted, adherence to the drugs does not seem to be the giant problem I thought it was. I was mistaken and had fallen victim to the misconception that it is rife in Africa. But the rising TB problem is reducing adherence.

I had a look at the meta-analysis, it has a lot of really obvious weaknesses. Firstly it is two years old. Some of the studies they include in their meta analysis are 6 years old. This is too old for most biol/med papers but particularly for this issue - the situation in Africa has changed a fair bit over this amount of time (in one way for the good - better access to ART) in no small part due to the rise in TB cases. Because of this, I would guess this meta analysis is not reflective of the current situation.

Massive problem - over half of the data in both N America and African was self-report. Self-report isn't worth the paper it's written on in science. Patients lie, or are mistaken - just not reliable at all.

Another weakness was highlighted in the comments at the bottom of the paper (which seem to be written by one of the authors as he refers to the article as 'our review') even say:

"The African studies in these analyses were conducted in patients with early access to limited therapy and are possibly not generalizable to the larger HIV epidemic in Africa. Furthermore, most African studies include patients during early therapy when they are experiencing dramatic increases in health status and before they develop long-term adverse effects of therapy"

Also, this study suffers from a problem that is endemic in meta analysis studies (and it is why they aren't always taken completely seriously..unless they are faultless with their statistical analysis and data selection techniques) - they rarely yield reliable, conclusive results. Firstly, it's very difficult to use studies where variables were measured equally using the same standardised measures. This is rare in clinical studies especially when the variable is a behavioural one, it is much easier in the 'purer' sciences like biochem/chem etc. Keeping all conditions constant in a study is very important if the results are to be conclusive. For example, did all of these studies use the same criteria to determine 'adherence'??

Another problem with them is that sources of bias are not controlled by the method. An amazing meta-analysis of badly designed studies will still give you crap results. You can avoid this by only including methodologically sound studies in a meta-analysis --> 'best evidence meta-analysis' but that is amazingly hard and I'll admit I did not have the compulsion to read every single study they used and evaluate it's statistical methods, statistical analysis is draining on the soul. I did however notice that they considered non–peer-reviewed articles - which is worrying.

Not all research is good research, unfortunately. I'm no expert at evaluating the merits of studies, takes years of experience - but that is my two cents worth anyway.

That wasn't as fun, or interesting, but definitely just as scary - statistical analysis makes me die a little inside.

Also, we don't really have to talk about this seeing as I'm guessing it's not really relevant to many people on this board

I don't know much about PrEP but it is my understanding that it makes you REALLY ill??? Surely there is a better way....

HOW on earth was this offensiveI'm completely lost hereDo you mean to imply that it is offensive for me to speculate about anything I haven't personally experienced? How ridiculous. How would anything progress in the world if that were the normAnd I'd like to point out that I said 'it is my understanding' I didn't say OH LOOK IT'S A FACT

Actually never mind, I've decided to not post here anymore. Most of my posts seem to offend/bother people and that was never my intention so it seems rather pointless. I really do wish you all the best of luck though!